Journal article
An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
European Journal of Pharmacology, Vol.353(1), pp.23-31
Jul/1998
Abstract
2-Arachidonoyl-glycerol (2-Ara-G1) has been isolated from various tissues and identified as an endogenous ligand for both cannabinoid receptors, CB1 and CB2. Here we report that in spleen, as in brain and gut, 2-Ara-G1 is accompanied by several 2-acyl-glycerol esters, two major ones being 2-linoleoyl-glycerol (2-Lino-G1) and 2-palmitoyl-glycerol (2-Palm-G1). These two esters do not bind to the cannabinoid receptors, nor do they inhibit adenylyl cyclase via either CB1 or CB2; however, they significantly potentiate the apparent binding of 2-Ara-G1 and its apparent capacity to inhibit adenylyl cyclase. Together these esters also significantly potentiate 2-Ara-G1 inhibition of motor behavior, immobility on a ring, analgesia on a hot plate and hypothermia caused by 2-Ara-G1 in mice. 2-Lino-G1, but not 2-Palm-G1, significantly inhibits the inactivation of 2-Ara-G1 by neuronal and basophilic cells. These data indicate that the biological activity of 2-Ara-G1 can be increased by related, endogenous 2-acyl-glycerols, which alone show no significant activity in any of the tests employed. This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity. (C) 1998 Elsevier Science B.V. All rights reserved.
Details
- Title
- An entourage effect; inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
- Creators
- S Ben-Shabat (null)E Fride (null)T Sheskin (null)T Tamiri (null)MH Rhee (null)Zvi Vogel (null) - The Weizmann Institute of ScienceT Bisogno (null)Petrocellis, L De Petrocellis (null)Marzo, V Di Marzo (null)R Mechoulam (null)
- Resource Type
- Journal article
- Publication Details
- European Journal of Pharmacology, Vol.353(1), pp.23-31; Jul/1998
- Number of pages
- 9
- Language
- English
- DOI
- https://doi.org/10.1016/S0014-2999(98)00392-6
- Scientific Unit
- The Weizmann Institute of Science
- Record Identifier
- 993265069303596
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